Application of the Nosé−Hoover Chain Algorithm to the Study of Protein Dynamics

Abstract

We have implemented the Nosé−Hoover chain (NHC) method combined with an explicit reversible integrator into the MD module of AMBER (i.e., SANDER) to study the dynamics and the structure of biopolymers. We have implemented both constant temperature (NVT) and constant temperature and pressure (NTP) methods. We have studied the structure and dynamics of the antifreeze protein (AFP) in the gas phase and when solvated by water. Single and multiple chains of thermostats attached to the solute, solvent, and simulation box (in the case of constant-pressure simulations) were examined. The simulation results from constant energy, Berendsen constant temperature and pressure and Nosé−Hoover chain NVT and NTP methods indicate all these methods can evolve the system to equilibrium at a comparable rate. The NHC method controls temperature better over the other methods. In particular, separate thermostat chains can eliminate the cold solute−hot solvent problem. For the constant temperature and pressure simulations, the NHC method gives volume fluctuations that are in good agreement with the experimentally determined isothermal compressibility. The volume probability distribution of a system consisting of one free particle obtained using the NHC method agrees with the exact distribution very well. However, that obtained from the Berendsen method does not allow fluctuations to occur, and the average volume approaches the most probable value exponentially. The contribution of different types of interactions to the pressure is examined. We show that the potential energy of the bond angle and dihedral angle does not contribute to the virial calculated using an atom representation. We also note that the intermolecular interactions tend to deform the water molecules. Therefore, the H−O bond lengths of water molecules are longer and the H−H distance is shorter than the values set in the potential model if no bond constraints are present. This effect results in a large negative contribution to pressure due to the bond potential or constraint force.